Obesity refers to excess accumulation and/or abnormal distribution of fat in body, increased body mass, and is a multifactorial chronic metabolic disease, and incidence of obesity increases year by year due to genetic factors, reduction of physical activity and so on. Obesity as a universal endocrine metabolic disease not only is a worldwide epidemic disease threating human health, but also is closely associated with hyperlipemia, hypertension, diabetes, coronary heart disease and so on (H E Ren, et al., Drug therapy of obesity and advance thereof, Strait Pharmaceutical Journal, 2011, 23(1):88-90). Thus, it is very important to perform prevention and treatment of obesity. At present, means for prevention and treatment of obesity mainly include dietary therapy, sports therapy, drug therapy and surgery. For patients with mild obesity, diet control and sports are effective; but for patients with moderate or more serious obesity, weight loss is a long term procedure, dietary and sports therapy alone usually could not solve the problem, and drug therapy is necessary in such situations.
At present, drug for prevention and treatment of obesity are mainly appetite suppressants, especially central appetite suppressants, such as amphetamine, amfepramone, synephrine, fenfluramine, sibutramine as well as fluoxetine among antidepressants, and lipase inhibitor orlistat (trade name: Xenical). However, the above drugs all have adverse reaction or toxic and side effects in different extents, such as cardiovascular system dysfunction, cardiac valves dysfunction, arrhythmia, pulmonary hypertension, respiratory system dysfunction, etc.
Synephrine hydrochloride (1-(4-hydroxyphenyl)-2-(methylamino)-ethanol hydrochloride, also called as deoxyepinephrine) (Formula I) has been recorded in the pharmacopeias of three countries of northern Europe and Pharmacopoeia Germanica, and is an epinephrine a-receptor stimulant having certain simulation effects on heart receptor. Synephrine has effects of constricting blood vessels and raising blood pressure, as well as effects of expanding trachea and bronchia, and is used in clinic for treatment of bronchial asthma, hypotension during operation and anesthetization, collapse and shock, postural hypotension. In addition, synephrine can enhance metabolism, increase heat exhaustion, and elevate energy level and oxidation of fat, so that synephrine is also often used as an effective ingredient of weight-loss medicines. Since ephedra plants are forbidden by Food and Drug Administration (FDA) of US in 2004, synephrine is used as a substitute for ephedra plants by dietary supplement manufacturers. It has been reported that when synephrine or ephedrine was administered simultaneously with caffeine and other stimulants, adverse reactions such as dizziness, shivering, headache, arrhythmia, epilepsy, mental diseases, heart diseases and stroke may occur.

Topiramate (2,3,4,5-bis-O-(1-methylethylene)-β-D-fructopyranose sulfamate) (Formula 2) is a broad spectrum nerve therapeutic agent approved by FDA in 1995, and has been used in clinic for many years for treatment of some epileptic seizures and prevention of migraine headache (E. Faught, et al., (1996) Neurology 46:1684-1690), and many documents disclosed the good therapeutic effects of topiramate in treatment of diabetes (U.S. Pat. No. 7,109,174B2 and U.S. Pat. No. 6,362,220B1), dysneuria (U.S. Pat. No. 6,908,902B2), depression (U.S. Pat. No. 6,627,653B2), mental disorders (U.S. Pat. No. 6,620,819B2), headache (U.S. Pat. No. 6,319,903B1) and hypertension (U.S. Pat. No. 6,201,010B1).
